Phase II Trial of a GM-CSF-producing and CD40L-expressing Bystander Cell Line Combined With an Allogeneic Tumor Cell–based Vaccine for Refractory Lung Adenocarcinoma

Abstract

We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized that the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given q14 days x3, followed by monthly x3. Cyclophosphamide (300 mg/m2 IV) was administered before the 1st and 4th vaccines to deplete regulatory T-cells. All-trans retinoic acid was given (150/mg/m2/day) after the 1st and 4th vaccines to enhance dendritic cell differentiation. Twenty-four participants were accrued at a single institution from 10/2006 to 6/2008, with a median age 64 and median of 4 previous lines of systemic therapy. A total of 101 vaccines were administered. Common toxicities were headache (54%) and site reaction (38%). No radiologic responses were observed. Median overall survival (OS) was 7.9 months (mo) and median progression-free survival (PFS) was 1.7 mo. Of 14 patients evaluable for immunological study, 5 had peptide-induced CD8+ T-cell activation after vaccination. Overall, vaccine administration was feasible in an extensively pretreated population of metastatic lung cancer. Despite a suggestion of clinical activity in the subset with immune response, the trial did not meet the primary endpoint of inducing radiologic tumor regression.

Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma

“…Clinical use of GM-K562 cells as bystander producers of GM-CSF has been reported previously in the context of vaccination of patients with advanced lung cancer(24, 25) and in patients with chronic lymphocytic leukemia (CLL)(25). In the CLL study, 22 subjects were treated with irradiated autologous tumor cells mixed with 1 × 10 7 GM-K562 cells without adverse events.…”

“…Plautz, et al reported adoptive T-lymphocyte transfer in glioblastoma patients, using cells harvested from inguinal lymph nodes harvested 8 – 10 days after a single subcutaneous injection of irradiated autologous tumor cells mixed with 500 micrograms of recombinant GM-CSF(25). More recently, Ishikawa described safe treatment with autologous formalin-fixed tumor vaccine in patients with newly diagnosed glioblastoma(26).…”

A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma

“…The GM.CD40L bystander cell line [14] and the NCI-H1944 and NCI-H2122 cell lines [10] were prepared as previously described. Vaccines were produced as previously described with minor changes [10].…”

“…Vaccines were produced as previously described with minor changes [10]. Ad-CCL21 (a replication-defective adenovirus vector propagated in E1A complementing cell lines) was obtained from NCI-Frederick.…”

Retinoid Chemoprevention: Who Can Benefit?

“…The median progression-free survival was 1.7 months and the median overall survival was 7.9 months. There was no radiologic tumor regression achieved [78]. …”